Magnetic resonance elastography （MRE） has become an important tool for the diagnosis and staging of fibrosis in metabolic dysfunction-associated fatty liver disease （MAFLD）， and its high diagnostic accuracy can help to effectively evaluate the dynamic changes and long-term prognosis of fibrosis in patients with MAFLD. In addition， MRE also shows wide potential in patient screening and outcome assessment in new drug development for metabolic-associated steatohepatitis. This article comprehensively analyzes the potential value of MRE in evaluating liver fibrosis in MAFLD patients， as well as its advantages in clinical practice and future development directions.

ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point， this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding， 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups （10 mice per group）： The 12-month-old control group （12MCON）， the 15-month-old control group （15MCON）， and the 15-month-old group with a high-fat diet （15MHFD）. The 12MCON and 15MCON groups were continuously fed a standard diet， while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups （10 mice per group）： the 20-month-old control group （20MCON）， the model group， and the low-， medium-， and high-dose Liangyi Paste groups （2.91 ， 5.82 ， 11.64 g·kg^-1·d^-1， respectively）. The 20MCON group was continuously fed a standard diet， while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age， the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage， while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage （when the mice reached 20 months of age）， tissue samples were collected. Hepatic TG levels were measured using assay kits； liver histology and lipid deposition were observed via hematoxylin-eosin （HE） and oil red O staining； reactive oxygen species （ROS） were detected by enzyme-linked immunosorbent assay （ELISA）； Cu²⁺， superoxide dismutase （SOD）， and malondialdehyde （MDA） levels were measured by colorimetry； mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction（Real-time PCR） and Wes automated protein expression system. ResultsCompared with 12MCON， the 15MCON group showed significantly increased hepatic TG， Cu²⁺， ROS， and MDA levels （P<0.01）， decreased SOD （P<0.01）， hepatocyte swelling， and disordered arrangement. The mRNA and protein levels of ferredoxin 1 （FDX1）， dihydrolipoamide S-acetyltransferase （DLAT）， heat shock protein 70 （HSP70）， dihydrolipoamide dehydrogenase （DLD）， pyruvate dehydrogenase E1 subunit-β （PDHB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and peroxisome proliferator-activated receptor γ （PPARγ） were significantly elevated （P<0.05， P<0.01）. Compared with 15MCON group， the 15MHFD and 20MCON groups exhibited further increases in TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group， and no significant lipid deposition was observed in the 20MCON group. FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and protein levels were significantly increased （P<0.05， P<0.01）. Compared with 20MCON group， the model group demonstrated markedly elevated TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， severe hepatic steatosis， and upregulated expression of FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and proteins （P<0.05， P<0.01）. All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.

OBJECTIVE: To explore the prenatal and postnatal phenotypes of 22q11.2 microdeletion syndrome (22q11.2DS) and enhance clinical understanding of this condition. METHODS: Data were collected from 86 fetuses diagnosed with 22q11.2DS at four prenatal diagnostic centers across China between January 2014 and August 2025. Prenatal imaging findings, pregnancy outcomes, and postnatal conditions were analyzed. RESULTS: Among the 86 fetuses, complete ultrasound data were available for 65 cases. Cardiovascular abnormalities were observed in 42 cases, thymic hypoplasia or aplasia in 7 cases, urinary system anomalies in 6 cases, nuchal translucency (NT) thickening in 7 cases, butterfly vertebrae, clubfoot, omphalocele and diaphragmatic hernia in 1 case each, cleft lip and palate in 2 cases, and ultrasound soft markers in 13 cases. The parents of 9 fetuses opted to continue with the pregnancy. Among these, 6 showed no significant ultrasound abnormalities and no related phenotypes postnatally, while the remaining 3 exhibited ultrasound anomalies with postnatal manifestations including developmental delay, immunodeficiency, and cardiac defects. CONCLUSION Fetuses with 22q11.2DS may exhibit various ultrasound abnormalities in multiple systems before and after birth. In addition to cardiovascular anomalies, they may also present with thymic hypoplasia or aplasia, thickened NT, and urinary abnormalities. Fetuses with thickened NT or thymic anomalies should be closely monitored, and thymic assessment should be included in routine prenatal imaging evaluations. For fetuses with 22q11.2DS who show no ultrasound abnormalities, the risk of developing severe phenotypes after birth is relatively low, but occult palate clefts and psychiatric disorders cannot be ruled out. Due to limitations in sample size and follow-up duration, above conclusions require further validation through large-scale prospective studies.
Humans ; Female ; Pregnancy ; Ultrasonography, Prenatal ; DiGeorge Syndrome/genetics* ; Adult ; Male ; Follow-Up Studies ; Fetus/diagnostic imaging* ; Phenotype ; Infant, Newborn

Objective To compare the clinical efficacy and safety differences between the triple immunosuppressive regimen of mizoribine (MZR) or mycophenolate mofetil (MMF) combined with tacrolimus (Tac) and glucocorticoids of kidney transplant recipients in one year after transplantation. Methods A single-center retrospective cohort study design was adopted. The clinical data of 156 patients who underwent the first allogeneic kidney transplantation at the Third Hospital of Peking University from January 2022 to December 2024 were included. The patients were divided into the MZR group (78 cases) and the MMF group (78 cases) based on the initial immunosuppressive regimen after transplantation. The baseline data, medication use in one year after transplantation, blood routine indicators, adverse events and clinical outcomes were compared between the two groups. For the repeated-measurement longitudinal data, repeated-measurement analysis of variance was used to evaluate the main effects of the groups, time and their interaction effects. Results At the primary efficacy endpoint, there were no statistically significant differences in the one-year survival rate, graft survival rate and incidence of acute rejection between the two groups (all P > 0.05). In terms of medication patterns and laboratory test indicators, there were significant time main effects and "time × group" interaction effects for Tac dosage (all P < 0.05). The Tac dosage in the MZR group was lower than that in the MMF group from 2 to 3 months after transplantation, and it was higher in the MZR group than in the MMF group from 7 to 12 months and one year after transplantation. White blood cell count in the MZR group was higher at one month after transplantation, and the platelet count was higher one year after transplantation (all P < 0.05). In terms of infection, the incidence of novel coronavirus and Pneumocystis jirovecii pneumonia infections in the MZR group was lower (all P < 0.05). In terms of metabolic indicators, the post-transplantation uric acid level was better in the MZR group than in the MMF group, but the total cholesterol level was higher one year after transplantation (all P < 0.05). In terms of liver function, there was a brief and mild increase in transaminase in the early stage after transplantation in the MZR group. Conclusions During the one-year follow-up after transplantation, both the MZR and MMF regimens demonstrate comparable immunosuppressive efficacy and overall safety in Chinese kidney transplant recipients. The MZR regimen shows clear advantages in reducing specific infection risks, alleviating bone marrow suppression and improving uric acid metabolism, but its potential impact on blood lipids needs to be monitored. Therefore, the MZR regimen may be an effective and safe alternative immunosuppressive option for kidney transplant recipients, especially those with high infection risk, poor hematological tolerance, or comorbid hyperuricemia.

Objective To analyze the technical essentials of single-microport assisted micro-uni-port thoracoscopic surgery, and to investigate its surgical efficacy and promotional value. Methods Clinical data of patients who consecutively underwent radical upper lobectomy in the Department of Thoracic Surgery of Xi'an International Medical Center Hospital from March 2023 to June 2024 were retrospectively analyzed. According to the surgical approach, patients were divided into two groups: the single-microport assisted group (underwent upper lobectomy via single-microport assisted micro-uni-port thoracoscopy) and the traditional uniportal group (underwent traditional uniportal thoracoscopic lobectomy). Clinical outcomes were compared between the two groups. Results A total of 62 patients were enrolled. There were 30 patients in the single-microport assisted group, with a mean age of (57.4±10.8) years, and 32 patients in the traditional uniportal thoracoscopic group, with a mean age of (57.6±8.7) years. The baseline data were comparable between the two groups. All patients in both groups successfully underwent minimally invasive surgery without conversion to thoracotomy. The operative time in the single-microport assisted group was significantly shorter than that in the traditional uniportal group [(146.03±30.79) min vs. (171.41±36.41) min, P=0.004]. However, there were no statistically significant differences between the two groups in intraoperative blood loss, number of dissected lymph nodes, duration of chest tube drainage, postoperative pain score, postoperative hospital stay, hospitalization cost, or incidence of postoperative complications (all P>0.05). Conclusion Single-microport assisted micro-uni-port thoracoscopic surgery for upper lobectomy can maximally integrate the advantages of three-port and uni-port VATS while effectively avoiding their disadvantages. It significantly shortens the operative time without increasing postoperative pain or complications, and represents a more minimally invasive, safer, and more convenient surgical approach.

ObjectiveTo investigate the effects of Ditantang on metabolic dysfunction-associated fatty liver disease （MAFLD） in rats by focusing on the regulation of glycogen synthesis mediated by the uridine diphosphate glucose （UDPG）-site-1-protease （S1P）-sterol regulatory element-binding protein （SREBP） axis. MethodsMAFLD was modeled in SD rats by feeding a high-fat diet for 12 weeks. Rats were randomized into a control group， a model group， low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg^-1·d^-1， respectively） Ditantang groups， and a positive control （Yishanfu， 0.18 g·kg^-1·d^-1） group. Starting from week 9 of modeling， each treatment group received corresponding drug interventions via gavage. After the experiment， the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured. The levels of TG， non-esterified fatty acids （NEFA）， glycogen， glucose-6-phosphate （G6P）， glucose-1-phosphate （G1P）， and UDPG in the liver tissue samples were measured by biochemical assay kits. Liver pathological morphology and lipid/glycogen deposition were observed via hematoxylin-eosin （HE） staining， oil red O staining， and Periodic acid-Schiff （PAS） staining. Immunofluorescence assay was conducted to detect the expression and localization of phosphoglucomutase-1 （Pgm1） and UDP-glucose pyrophosphorylase 2 （Ugp2） in the rat liver. Real-time PCR and Western blot were employed to quantify mRNA and protein levels， respectively， of key glycogen synthesis enzymes （Pgm1 and Ugp2）， key lipogenesis-related transcription factor SREBP and its target genes ［acetyl-CoA carboxylase （ACC）， fatty acid synthetase （FASN）， and stearoyl-CoA desaturase （SCD1）］， as well as S1P. ResultsCompared with the control group， the model group exhibited elevated levels of TC， TG， LDL-C in the serum and TG and NEFA in the liver， decreased serum HDL-C level （P<0.01）， reduced hepatic levels of G1P， G6P， UDPG， and glycogen （P<0.01）， appearance of fat vacuoles of varying sizes and abundant red lipid droplets， with prominent lipid deposition and reduced areas of deep glycogen staining in the liver tissue， upregulated mRNA and protein levels of SREBP1， S1P， ACC， FASN， and SCD1 （P<0.01）， and downregulated mRNA and protein levels of Pgm1 and Ugp2 （P<0.01）. Compared with the model group， all doses of Ditantang reduced the levels of TC and TG in the serum and TG and NEFA in the liver， while elevating the serum HDL-C level. Additionally， medium- and high-dose Ditantang reducted the LDL-C level （P<0.05）. Ditantang at all doses increased the hepatic levels of G1P， G6P， UDPG， and glycogen， alleviated hepatic steatosis and lipid deposition， enhanced glycogen storage， downregulated the mRNA and protein levels of SREBP1， S1P， ACC， FASN， and SCD1 （P<0.05）， while upregulating the expression of Pgm1 and Ugp2 （P<0.01）. Immunofluorescence analysis revealed decreased fluorescence intensity of S1P and enhanced fluorescence intensity of Ugp2 （P<0.01）. ConclusionDitantang can regulate glycogen synthesis through the UDPG-S1P-SREBP axis to prevent and treat MAFLD.

Objective:To investigate the clinical features, treatment strategies, and prognosis of pediatric Castleman disease (CD), with the aim of enhancing disease recognition and improving diagnostic and therapeutic approaches.Methods:A retrospective analysis was conducted on the clinical data of 29 children diagnosed with CD at the Children′s Hospital, Zhejiang University School of Medicine, between January 2016 and January 2024. Age, sex, initial presentations, routine blood test, inflammatory indicators, coagulation function test, immunoglobulin level, histopathological examination, imaging examination, treatment and follow-ups were recorded. Patients were classified into two groups based on the presence or absence of symptoms: the symptomatic Castleman disease group (SC) and the asymptomatic Castleman disease group (AC). All patients were followed for a minimum of six months. Clinical characteristics, therapeutic regimens, and outcomes were compared between the two groups.For the measurement information, the independent samples t test was used for comparison between groups of data that conformed to normal distribution; the Mann-Whitney U test was used for comparison between groups of data that did not conform to normal distribution. The Chi-square test or Fisher′s exact probability method was used for comparison between groups of count data. Results:A total of 29 pediatric CD cases were included, comprising 15 males and 14 females. The number of patients diagnosed as unicentric Castleman disease (UCD) was 21, with the rest 8 as multicentric Castleman disease (MCD). There were 11 patients (37.9%) in the SC group and 18 patients (62.1%) in the AC group. The median age at onset was 10.0 years (interquartile range: 6.5-12.2 years). The most common initial presentation was mass ( n=20), followed by fever ( n=2), amaemia ( n=2), fever with fatigue ( n=2), rash ( n=1), abdominal pain ( n=1), and cough ( n=1). The frequently involved sites were neck ( n=8), abdominal cavity ( n=5), mediastinum ( n=3), retroperitoneum ( n=2), and one case each in the back, upper arm, and pelvis. The maximum lesion volume reached 1 040 cm 3. Compared to the AC group, the SC group had significantly lower hemoglobin levels [108.0(92.0, 123.0)g/L vs. 127.0(117.5, 139.0)g/L, Z=-2.35, P=0.019] and significantly higher levels of C-reactive protein (CRP) [38.0(3.0, 87.0)mg/L vs. 0.6(0.5, 3.8)mg/L, Z=-2.19, P=0.029], prothrombin time[12.6(11.4, 13.3)s vs. 11.3(10.5, 11.7)s, Z=-2.64, P=0.008], and fibrinogen [4.5(3.5, 5.4)g/L vs. 2.1(1.9, 2.6)g/L, Z=-3.04, P=0.002]. All patients underwent MRI/CT and ultrasonography; however, only 2 cases were diagnosed as CD by ultrasound. All patients underwent surgical excision of the mass, and diagnoses were confirmed by histopathological examination. Among the SC group, 4 patients (4/11, 36.4%) required postoperative treatment with glucocorticoids alone or in combination with immunosuppressants and biologics. The overall prognosis was favorable, with follow-up ranging from 6 months to 7 years and no reported mortality. One case, initially misdiagnosed as systemic lupus erythematosus, was later confirmed to be CD complicated with paraneoplastic pemphigus (PNP); this patient experienced recurrent fever, rash, and elevated CRP, and continued to require low-dose glucocorticoids and tacrolimus during the 4-year follow-up. Conclusion:In chileren, CD is most common in the neck and surgical resection yields favorable outcomes. Approximately 37.9% of patients present with systemic symptoms, of which about 36.4% require postoperative systemic therapy such as glucocorticosteroids. CD complicated with PNP may be misdiagnosed. Symptomatic cases are often associated with anemia, elevated CRP levels, and coagulation abnormalities. UCD pediatric patients without complications have a good prognosis and there′s no need for long-term medications after surgery. About 37.5% of MCD pediatric patients require glucocorticoids, immunosuppressants, biotherapy or chemotherapy to control symptoms in the postoperative period. Imaging modalities have limited diagnostic value, and histopathological examination remains the gold standard for diagnosis.

Objective:To investigate the role of RNA helicase DDX5 in renal interstitial fibrosis and its potential mechanism, and provide possible molecular target for the diagnosis and treatment of renal interstitial fibrosis.Methods:The animal and cell models of unilateral ureteral obstruction (UUO) and DDX5-pharmacological and genetic blocking were established. Twenty-four male mice aged 6-8 weeks and weighting about 18-22 g were divided into sham operation group, UUO group, sham operation+RX5902 group and UUO+RX5902 group by random number table method, with 6 mice in each group. Supinoxin (RX5902, a phosphorylated DDX5 inhibitor, 75 mg/kg) was administered by gavage in mice in the sham operation+RX5902 group and UUO+RX5902 group on day 0 and day 3 after the operation, respectively. The mice were sacrificed to collect kidney specimens one week after the surgery. The human renal tubular epithelial cell line (HK-2 cells) was routinely cultured and divided into control group, scramble siRNA group, DDX5 siRNA group, TGF-β1 group, scramble siRNA+TGF-β1 group and DDX5 siRNA +TGF-β1 group. The dosage of RX5902 was 20 nmol/L, and the dosage of transforming growth factor-β1 (TGF-β1) was 10 ng/ml. HE staining and Masson staining were used to evaluate renal tubule injury and collagen fiber deposition. Western blotting, immunofluorescence and immunohistochemistry were used to detect the protein expression levels of DDX5 and fibrosis-related indexes such as fibronectin and α-smooth muscle actin (α-SMA). The flow cytometry was used to detect the cell cycle. Results:In comparison to sham operation group, UUO group exhibited significantly elevated protein expression levels of fibronectin, α-SMA and DDX5 in kidney tissues (all P<0.05), accompanied by notable nuclear translocation of DDX5. TGF-β1 stimulation facilitated the upregulation of fibronectin, α-SMA, and DDX5 expression, as well as DDX5 nuclear translocation in HK-2 cells (all P<0.05). Pharmacological and genetic inhibition of DDX5 attenuated UUO or TGF-β1-induced elevated protein levels of fibronectin and α-SMA. Compared with scramble siRNA+TGF-β1 group, DDX5 siRNA+TGF-β1 group exhibited reduced protein expression levels of fibronectin, α-SMA and DDX5 in HK-2 cells (all P<0.05). Compared with UUO group, UUO+RX5902 group showed alleviation of renal epithelial cell exfoliation, renal tubule atrophy or lumen dilation and decreased scores of both tubular injury and interstitial collagen deposition, along with reduced protein expression levels of fibronectin, α-SMA and DDX5 (all P<0.05). Similarly, RX5902 inhibited TGF-β1-induced fibrotic responses in HK-2 cells (all P<0.05). Flow cytometry analysis results revealed that TGF-β1 stimulation resulted in a significant increase in the proportion of HK-2 cells in the G2/M phase. Conversely, silencing of DDX5 led to a significant reduction in the proportion of HK-2 cells in the G2/M phase (all P<0.05). Conclusions:DDX5 is significantly elevated in the renal tissues of UUO mice and TGF-β1-induced HK-2 cells. The pharmacological and genetic blockade of DDX5 can delay renal fibrosis by reducing cell cycle arrest and alleviating cell damage.

Objective:This current study aims to explore the approaches for constructing a professional clinical research system within the context of research ward development, with the ultimate objective of providing valuable guidance for the establishment and development of proficient clinical research teams.Methods:Through a comprehensive case analysis, integrating the practical experiences from clinical trials conducted in the research ward of a Class-A tertiary hospital in Beijing, along with an extensive review of relevant literature and policy studies, this paper examined the current state of domestic clinical research implementation teams. Subsequently, a series of strategies were devised to build and foster professional clinical research teams and to explore corrective measures for cultivating a dynamic professional clinical research talent ecosystem.Results:The development of full-time clinical research teams in China was rather slow, and there was a lack of mature clinical trial teams training blueprints. Drawing on the practical experience accumulated during the establishment of a professional clinical research team in a leading hospital in Beijing, it was crucial to attach utmost importance to the optimal allocation of human and material resources. This required the systematic training of principal investigators, coordinating researchers, and research assistants, as well as the setting up of a comprehensive support system, an advanced scientific research team, and a quality control unit. Moreover, the standardization of operational models of both domestic and foreign research institutions, along with the implementation of corresponding support and incentive mechanisms, and the strengthening of training and continuing education frameworks were equally significant.Conclusions:During the process of assembling a full-time clinical research team, it is of utmost significance to cultivate professional principal investigators, coordinating researchers, and research assistants. Complemented by the establishment of a comprehensive support team, a scientific research team, and a quality control team, along with corresponding support and incentive mechanisms, this is crucial for constructing a professional clinical research execution team and a sustainable talent ecosystem in the research ward. Eventually, this will drive the efficient and high-quality progress of China's pharmaceutical industry.

OBJECTIVE: To investigate the safety and prognostic factors influencing the treatment of upper urinary tract urothelial carcinoma (UTUC) combined with bladder cancer (BCa) by laparoscopic simultaneous radical cystectomy and nephroureterectomy (RCNU). METHODS: The clinical data of patients admitted to Peking University Third Hospital for laparoscopic RCNU surgery from January 2009 to September 2023 were analyzed retrospectively. Based on the same gender, age (±5 years), history of uroepithelial tumors, underlying diseases, T-stage, N-stage, M-stage, American Society of Anesthesiologists (ASA) score, Charlson comorbidity index, and body mass index (BMI) (±5), 34 patients with RCNU were matched 1 ∶1 with patients with bladder cancer who underwent laparoscopic radical cystectomy (RC) alone. Kaplan-Meier survival analysis was used to calculate patient survival, and Cox proportional regression risk model was used to analyze clinical factors affecting prognosis. RESULTS: Of the 68 patients enrolled, the follow-up rate was 100% with a median follow-up time of 27.0 (11.7, 60.2) months. Comparison of intraoperative conditions (including operation time, estimated intraoperative bleeding, intra-operative blood transfusion, etc.) between the two groups of patients showed no significant difference (P>0.05). Comparison of preoperative creatinine and postoperative creatinine between the two groups of patients showed significant differences (P < 0.05). The perioperative Clavien grade Ⅲ-Ⅳ complication rates were 2.9% (1/34) in the RC group and 5.9% (2/34) in the RCNU group. There was no significant difference in terms of perioperative complications between the two groups. Overall survival was significantly lower in the patients receiving RCNU compared with the matched group receiving RC alone (P < 0.05). Cox regression analysis suggested that two factors, high N stage and high postoperative creatinine, were independent risk factors affecting the prognosis of patients in the 2 groups (P < 0.05). CONCLUSION The overall survival prognosis of patients undergoing RCNU surgery was worse compared with laparoscopic RC surgery alone during the same period. There was no clinically significant difference between the two groups in terms of operation time, intraoperative bleeding, and perioperative complications, and there were clinically significant differences in preoperative renal function and post-operative renal function.
Humans ; Laparoscopy/methods* ; Nephroureterectomy/methods* ; Cystectomy/methods* ; Prognosis ; Male ; Retrospective Studies ; Female ; Urinary Bladder Neoplasms/mortality* ; Middle Aged ; Aged